生物谷報道：DNA元素百科全書協(xié)會（ENCODE）14日發(fā)表的一系列文章,，讓人們重新理解了人類基因組是如何發(fā)揮作用的,。ENCODE的研究指出，人類基因組是一個由基因,、調(diào)控元素以及某些非蛋白質(zhì)編碼DNA序列組成的復(fù)雜網(wǎng)絡(luò),，并以部分重疊的方式相互作用。這與基因組是一個個不連續(xù)基因規(guī)整組合的傳統(tǒng)觀點大相徑庭,。
2003年4月,，人類基因組計劃的完成是一項非常重要的成就，但只是人類利用基因信息來診斷,、治療和預(yù)防疾病的第一步,。有了人類基因組序列，就好比有了一本如何制造人體的指導(dǎo)手冊,，研究者還必須學(xué)會如何讀懂手冊,，這樣才能將每個部件搞清楚，理解這些部件是如何協(xié)同工作來影響人的健康,。
ENCODE協(xié)議是由美國基因組研究所和美國健康研究所組織的國際合作項目,，目標(biāo)是為人類基因組中所有具有關(guān)鍵生物功能的元素繪制一份全范圍的詳細(xì)目錄。第一階段是為期4年的試驗性研究,，主要是測試該項目的可行性,，這也是迄今為止第一次對基因組中所有類型的功能元素進(jìn)行的系統(tǒng)測定。這些元素包括蛋白質(zhì)編碼基因,、非蛋白質(zhì)編碼基因,、控制基因轉(zhuǎn)錄的調(diào)節(jié)元素、維持染色體結(jié)構(gòu)以及調(diào)控染色體復(fù)制的元素,。該研究聚焦于44個靶位,，總共占人類基因組序列的1％，也就是3000萬個DNA堿基對,。這些靶位是經(jīng)過精心選擇的有代表性的部分,，橫跨整個人類基因組序列。全世界35個研究小組參與了此項研究,，一共測得了200多個數(shù)據(jù)集,，分析了6億多個數(shù)據(jù)點,。
長期以來，人們一直認(rèn)為人類基因組是由一系列相對較小的不連續(xù)的基因組成,，還有大量沒有生物活性的無用DNA,。但EN鄄CODE的研究發(fā)現(xiàn)，人類基因組中的大多數(shù)DNA轉(zhuǎn)錄成功能性的分子RNA,，而且這些轉(zhuǎn)錄是廣泛重疊的,，無用的DNA序列很少。實際上,，人類基因組是一個交織復(fù)雜的網(wǎng)絡(luò),，基因只不過是眾多DNA序列中具有特定生物功能的一種。"我們對基因及其轉(zhuǎn)錄的看法有必要進(jìn)化,，"研究人員稱,，"基因組的網(wǎng)絡(luò)模型提出了一些很有趣的機(jī)械問題，需要進(jìn)一步研究才能回答,。"
ENCODE的另一發(fā)現(xiàn)有助于對基因組（特別是哺乳動物的基因組）進(jìn)化的理解,。直到最近，科學(xué)界還認(rèn)為絕大多數(shù)具有重要生物功能的DNA序列處于基因組中進(jìn)化受約束的區(qū)域,，也就是說它們極有可能是作為一個種群進(jìn)化的,。但新的研究發(fā)現(xiàn)，基因組中大約一半的功能元素在進(jìn)化過程中并未受到明顯的約束,，這表明許多基因包含有一個功能元素池,，這個元素池在進(jìn)化過程中可能會變成一個"自然選擇倉庫"，為每個種群提供其獨有的功能元素,。
ENCODE的研究成果發(fā)表在14日的英國《自然》以及6月份的《基因組研究》雜志上,。
FIGURE 1. Hidden message.
Ishihara's test for red–green colour deficiencies uses several coloured plates, similar to this one, in which a number is disguised in a different colour within the dot pattern. Similarly, we are so fascinated by genes (green dots) that we have become blinded to non-gene components (magenta dots) of the genome. However, in studying 1% of the genome, the researchers of the ENCODE consortium2 found that non-gene sequences have essential regulatory functions, and thus cannot be ignored.
原文出處：
Nature Volume 447 Number 7146
Genomics: Encyclopaedia of humble DNA p782
Researchers of the ENCODE consortium have analysed 1% of the human genome. Their findings bring us a step closer to understanding the role of the vast amount of obscure DNA that does not function as genes.
John M. Greally
doi:10.1038/447782a
Full Text | PDF (340K)
See also: Editor's summary
Genome Research Volume 17, Issue 6: June 2007
George M. Weinstock
ENCODE: More genomic empowerment
Genome Res. 2007 17: 667-668. [Full Text] [PDF] OPEN ACCESS ARTICLE
作者簡介：
John M. Greally, M.B.,B.Ch., Ph.D.
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
Assistant Professor, Department of Medicine (Hematology)
Assistant Professor, Department of Molecular Genetics
Professional Interests
Overview of Professional Interests
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More Information About Dr. John Greally
GreallyLab home page
George Weinstock, Ph.D.
Professor, Departments of Molecular and Human Genetics and Molecular Virology & Microbiology
Co-Director, Human Genome Sequencing Center
Adjunct Professor, Department of Microbiology and Molecular Genetics, UTHHSC
Adjunct Professor, Department of Health Informatics, UTHHSC
B.S., University of Michigan, 1970
Ph.D., Massachusetts Institute of Technology, 1977
Postdoc, Stanford University Medical School, 1980
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Last modified: October 2005
Research Interests Selected Publications Contact Information
RESEARCH INTERESTS:
George Weinstock received a B.S. from the Univ. Michigan (Biophysics, 1970) and a Ph.D. from MIT (Microbiology, 1977), studying transposition and gene control in phage P22, and constructing one of the first genomic physical maps. His postdoctoral research (Biochemistry Department, Stanford Univ. Medical School ) studied mechanisms of genetic recombination and enzymology of RecA protein. In 1980, he joined the NCI-Frederick Cancer Research Facility and established the DNA Metabolism Section, Laboratory of Recombinant DNA. In 1984, he moved to The Univ. Texas-Houston Health Science Center (Dept. Biochemistry and Molecular Biology, 1984-95; Dept. Microbiology and Molecular Genetics, 1995-2001). He applied molecular genetics and genomics to study infectious disease pathogens Escherichia coli, Treponema pallidum, and the enterococci. In 1998, he joined the BCM Human Genome Sequencing Center as Co-Director and became a tenured Professor in the Molecular and Human Genetics Department in 2001.
As Co-Director of the HGSC, he helped lead one of three NIH-funded large-scale Genome Centers involved in the Human Genome Project, completed in 2003. The HGSC was responsible for chromosomes 3, 12, and part of X in the HGP. Since then he has helped oversee a number of other HGSC genome projects: the rat, mouse, cow, macaque, sea urchin, honey bee, Drosophila melanogaster and pseudoobscura, Dictyostelium discoideum, which are complete or nearly so, and new projects the orangutan, wasp, acorn worm, Ascosphaera apis, and Acanthamoeba.
In addition he has continued to sequence bacterial genomes of interest in infectious diseases and evolutionary studies including Treponema pallidum (syphilis), periodontal pathogens Fusobacterium nucleatum and Treponema denticola, bioterroism agents Rickettsia typhi and Francisella tularensis, superbugs Enteroccus faecium and faecalis and Staphylococcus aureus, plant pathogen Pantoea stewartii, bovine pathogens Mannheimia haemolytica and Moraxella bovis, honey bee pathogen Paenibacillus larvae, and Bacillus pumilis (highly radiation resistant).
Sequenced genomes are analyzed and annotated. For eukaryotic genomes, this involves coordination of experts in gene prediction, evolutionary analysis, genome structure, and functional themes of interest for each organism. Genome assembly, annotation, and analysis involve sophisticated bioinformatics.
For bacterial genomes, this information is used for post-sequencing functional genomics. This includes cloning and expressing all genes into E. coli from a bacterium to identify functions, antigens, and vaccine candidates, making microarrays, or constructing null mutants in all members of gene families such as regulators or pumps. These are analyzed for virulence, antibiotic sensitivity, or other phenotypes.
Future projects focus on sequencing individuals with altered phenotypes, for disease gene discovery, or closely related bacteria to correlate phenotype with genotype. In both cases a deep survey of genetic variation is realized.
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SELECTED PUBLICATIONS:
1. Smajs D, McKevitt M, Howell JK, Norris SJ, Cai WW, Palzkill T, Weinstock GM (2005). Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection. J. Bacteriol. 187: 1866-1874.
2. Ross MT et al. (2005). The DNA sequence of the human X chromosome. Nature 434: 325-337.
3. Eichinger L, Pachebat JA, Glockner G, Rajandream MA, Sucgang R, Berriman M, Song J, Olsen R, Szafranski K, Xu Q, Tunggal B, Kummerfeld S, Madera M, Konfortov BA, Rivero F, Bankier AT, Lehmann R, Hamlin N, Davies R, Gaudet P, Fey P, Pilcher K, Chen G, Saunders D, Sodergren E, Davis P, Kerhornou A, Nie X, Hall N, Anjard C, Hemphill L, Bason N, Farbrother P, Desany B, Just E, Morio T, Rost R, Churcher C, Cooper J, Haydock S, van Driessche N, Cronin A, Goodhead I, Muzny D, Mourier T, Pain A, Lu M, Harper D, Lindsay R, Hauser H, James K, Quiles M, Madan Babu M, Saito T, Buchrieser C, Wardroper A, Felder M, Thangavelu M, Johnson D, Knights A, Loulseged H, Mungall K, Oliver K, Price C, Quail MA, Urushihara H, Hernandez J, Rabbinowitsch E, Steffen D, Sanders M, Ma J, Kohara Y, Sharp S, Simmonds M, Spiegler S, Tivey A, Sugano S, White B, Walker D, Woodward J, Winckler T, Tanaka Y, Shaulsky G, Schleicher M, Weinstock G, Rosenthal A, Cox EC, Chisholm RL, Gibbs R, Loomis WF, Platzer M, Kay RR, Williams J, Dear PH, Noegel AA, Barrell B, Kuspa A (2005). The genome of the social amoeba Dictyostelium discoideum. Nature 435: 43-57.
4. Richards S, Liu Y, Bettencourt BR, Hradecky P, Letovsky S, Nielsen R, Thornton K, Hubisz MJ, Chen R, Meisel RP, Couronne O, Hua S, Smith MA, Zhang P, Liu J, Bussemaker HJ, van Batenburg MF, Howells SL, Scherer SE, Sodergren E, Matthews BB, Crosby MA, Schroeder AJ, Ortiz-Barrientos D, Rives CM, Metzker ML, Muzny DM, Scott G, Steffen D, Wheeler DA, Worley KC, Havlak P, Durbin KJ, Egan A, Gill R, Hume J, Morgan MB, Miner G, Hamilton C, Huang Y, Waldron L, Verduzco D, Clerc-Blankenburg KP, Dubchak I, Noor MA, Anderson W, White KP, Clark AG, Schaeffer SW, Gelbart W, Weinstock GM, Gibbs RA (2005). Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution. Genome Res. 15: 1-18.
5. Seshadri R et al. (2004). Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proc. Natl. Acad. Sci. USA 101: 5646-5651.
6. Rat Genome Sequencing Project Consortium (2004). Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428: 493-521.
7. International Human Genome Sequencing Consortium (2004). Finishing the euchromatic sequence of the human genome.Nature 431: 931-945.
8. McLeod MP, Qin X, Karpathy SE, Gioia J, Highlander SK, Fox GE, McNeill TZ, Jiang H, Muzny D, Jacob LS, Hawes AC, Sodergren E, Gill R, Hume J, Morgan M, Fan G, Amin AG, Gibbs RA, Hong C, Yu XJ, Walker DH, Weinstock GM (2004). Complete Genome Sequence of Rickettsia typhi and Comparison with Sequences of Other Rickettsiae. J. Bacteriol. 186: 5842-5855.
9. Gibbs RA, Weinstock GM (2003). Evolving methods for the assembly of large genomes. In Cold Spring Harbor Symp. Quant. Biol. Cold Spring Harbor Press, Cold Spring Harbor, NY, Vol. LXVIII, pp. 189-194.
For more publications, see listing on Pub Med.
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